The effects of a point mutation of the β2 subunit of GABAA receptor on direct and modulatory actions of general anesthetics
| Autor: | Takashi Mashimo, Ichiro Uchida, Ikuto Yoshiya, Makoto Takenoshita, Sakae Fukami |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Pentobarbital Anesthetics General Phenylalanine Protein subunit Voltage clamp Pharmacology Membrane Potentials GABAA-rho receptor Mice Xenopus laevis Chloride Channels Etomidate Internal medicine medicine Animals Hypnotics and Sedatives Point Mutation GABA Modulators Receptor Propofol gamma-Aminobutyric Acid Dose-Response Relationship Drug GABAA receptor Chemistry Receptors GABA-A Endocrinology Amino Acid Substitution Mechanism of action Oocytes Tyrosine medicine.symptom medicine.drug |
| Zdroj: | European Journal of Pharmacology. 368:269-276 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(99)00033-3 |
| Popis: | The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in the direct and modulatory actions of general anesthetics remain to be elucidated. The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit was reported to reduce sensitivity to activation by GABA, but not pentobarbital. We examined whether this mutation of the beta2 subunit (Tyr157--Phe) affects the direct and modulatory actions of other general anesthetics such as propofol and etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s subunits. The mutation of the beta2 subunit reduced the apparent affinity for propofol. However, the mutation had no effect on both the direct actions of pentobarbital and etomidate or on the modulatory actions of pentobarbital, propofol and etomidate. These results suggest that unique loci may exist for the direct action of propofol and that the GABA binding site may not mediate the modulatory actions of general anesthetics at GABA(A) receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect